Explore the vast range of titles available.

Previous studies have indicated that cytochrome P450s (CYPs) are involved in the metabolism of polybrominated diphenyl ether (PBDE) flame retardants in humans, resulting in the formation of hydroxylated PBDEs (OH-PBDEs) that are potentially more toxic than the parent PBDEs. However, the specific enzymes responsible for the formation of OH-PBDEs are unknown. The purposes of this study were to characterize the in vitro metabolism of 2,2´,4,4´-tetrabromodiphenyl ether (BDE-47) by human liver microsomes (HLM) and recombinant human CYPs, and to identify the CYP(s) that are active in the oxidative metabolism of BDE-47. Recombinant human CYPs (CYP1A1, 1A2, 1B1, 2A6, 2B6, 2C8, 2C9, 2C19, 2D6, 2E1, and 3A4) were incubated with BDE-47 (20 µM), and the metabolites were measured and characterized using gas chromatography with tandem mass spectrometry (GC-MS/MS). For kinetic studies, CYP2B6 and pooled human liver microsomes (HLMs) were incubated with BDE-47 (0-60 µM). CYP2B6 was the predominant CYP capable of forming six OH-BDEs, including 3-OH-BDE-47, 5-OH-BDE-47, 6-OH-BDE-47, 4-OH-BDE-42, 4´-OH-BDE-49, and a metabolite tentatively identified as 2´-OH-BDE-66. On the basis of full-scan GC-MS analysis, we hypothesized the formation of two other metabolites: di-OH-tetra-BDE and di-OH-tetrabrominated dioxin. In kinetic studies of BDE-47 metabolism by CYP2B6 and pooled HLMs, we found Km values ranging from 3.8 to 6.4 µM and 7.0 to 11.4 µM, respectively, indicating the high affinity toward the formation of OH-BDEs. Our findings support a predominant role of CYP2B6 in the metabolism of BDE-47 to potentially toxic metabolites, including a hypothesized di-OH-tetrabrominated dioxin metabolite. These results will assist future epidemiological studies investigating the potential of PBDEs and their metabolites to produce neurobehavioral/neurodevelopmental disorders.

Semi-volatile organic contaminants (SVOCs) are known for their tendency to evaporate from source regions and undergo atmospheric transport to distant areas. Cold condensation intensifies dry deposition, particle deposition, and scavenging by snow and rain, allowing SVOCs to move from the atmosphere into terrestrial and aquatic ecosystems in alpine and polar regions. However, no standardized methods exist for the sampling, laboratory processing, and instrumental analysis of persistent organic pollutants (POPs) in snow. The lack of reference methods makes these steps highly variable and prone to errors. This study critically reviews the existing literature to highlight the key challenges in the sampling phase, aiming to develop a reliable, consistent, and easily reproducible technique. The goal is to simplify this crucial step of the analysis, allowing data to be shared more effectively through standardized methods, minimizing errors. Additionally, an innovative method for laboratory processing is introduced, which uses activated carbon fibers (ACFs) as adsorbents, streamlining the analysis process. The extraction method is applied to analyze polychlorobiphenyls (PCBs) and chlorinated pesticides (α-HCH, γ-HCH, p,p′-DDE, o,p′-DDT, HCB, and PeCB). The entire procedure, from sampling to instrumental analysis, is subsequently tested on snow samples collected on the Svalbard Islands. To validate the efficiency of the new extraction system, quality control measures based on the EPA methods 1668B and 1699 for aqueous methods are employed. This study presents a new, reliable method that covers both sampling and lab analysis, tailored for detecting POPs in snow.

Brake wear emission is a significant contributor to vehicle-related particulate matter, especially in areas with high traffic density and braking frequency. Only recently, non-exhaust emissions from car brake wear have been regulated under Euro 7 regulation, which introduces emission limits for both brake and tires. It also introduces a standard brake particle assessment procedure which includes sampling procedure and measurement techniques defined in the Global Technical Regulation on brakes from light-duty vehicles up to 3.5 t. Over the years, various experimental setups have been tried leading to non-comparable results. The brake wear particle emissions, expressed as emission factors, are mostly estimated as particle mass or particle number and described using different units (e.g., mg/stop brake, mg/km brake; particle number/cm 3 ) making the comparison between studies very difficult. The aim of the present literature review is to present the state-of-the-art of different experimental methods tuned for assessing brake wear emissions, including electric vehicles. The experiments are carried in close, semi-closed, and open systems, and depending on the experimental design, different sampling methods are applied to reduce particle transport loss and guarantee the efficiency of the particle sampling. Driving condition (e.g., speed and applied pressure), formulation of brake materials, and friction temperature have been found to strongly affect the emission characteristics of brake particles, and this needs to be considered when designing study procedures. The findings reported in this review can be beneficial to policy makers and researchers.

Seventeen parent polycyclic aromatic hydrocarbons (PAHs) and 38 congeners of polychlorinated biphenyls were measured at five different sediment depths (between the surface and ~300 cm below the seafloor) at 160 sites in Naples harbour. Total PAH (ΣPAH) and PCB (ΣPCB) concentrations ranged between 0.012-21.73 ⁻ nd 0.001-0.222 mg kg ⁻ ¹, respectively. For PAHs, an evident and progressive decrease in concentration with depth documents the effects of a more intense anthropic impact of this group of pollutants in the recent period. A selected number of PAH isomer pairs (phenanthrene/anthracene, fluoranthene/pyrene and benzo(a)anthracene/crysene) were used to distinguish between contaminants of pyrolitic and petrogenic origin. More than 90% of PAHs present at the different depths of the studied sediments indicate pyrolitic industrial origins. On the other hand, relatively high concentrations of three- and four-ring PAHs suggest a limited contribution of vehicular emissions to the contamination of sediments. An unexpected and systematic increase of ΣPCB concentration, exceeding values approved by international regulations, was found in the studied sediments, testifying to the uncontrolled discharge to the studied area from industrial and commercial activity on nearby land. Ecotoxicological risk levels calculated for PAHs suggests a relatively elevated level of toxicity in surface sediments decreasing with depth and very low toxicity values associated to PCB toxicity.

The Isthmus of Tehuantepec corresponds to the shortest distance (~200 km) between the Gulf of Mexico and the Pacific Ocean in Southern Mexico, and the main economical activity of this region is oil extraction and refining. Polycyclic aromatic hydrocarbons (PAHs) and total petroleum hydrocarbons (TPHs) were determined in a 210 Pb dated sediment core collected from the continental shelf of Tehuantepec Gulf, in the vicinity of the oil refinery of Salina Cruz, Oaxaca, the main oil refining facility of the country. The sediments were mostly of coarse nature and hence PAHs and TPHs concentrations throughout the core (61–404 μg g −1 and 29–154 mg kg −1 , respectively) were below international quality benchmarks. Depth profiles of both PAHs and TPHs concentrations showed increasing trends since the early 1900s but the higher values were found from the 1950s to present. PAH congener ratios showed that these contaminants had both petrogenic and pyrolitic sources, although the former has been predominant since the 1970s. The Salina Cruz refinery started operations in 1978 but the oil industry activities in the Tehuantepec Isthmus go back to the beginning of the twentieth century with the operation of Minatitlan refinery in the Gulf of Mexico, and the Gulf of Tehuantepec being the main conduit for oil distribution in the Pacific coast. The observed changes in contaminant distributions described well the oil industry development in the area.

Rationale About 50% of hospitalized coronavirus disease 2019 (COVID-19) patients with diabetes mellitus (DM) developed myocardial damage. The mechanisms of direct SARS-CoV-2 cardiomyocyte infection include viral invasion via ACE2-Spike glycoprotein-binding. In DM patients, the impact of glycation of ACE2 on cardiomyocyte invasion by SARS-CoV-2 can be of high importance. Objective To evaluate the presence of SARS-CoV-2 in cardiomyocytes from heart autopsy of DM cases compared to Non-DM; to investigate the role of DM in SARS-COV-2 entry in cardiomyocytes. Methods and results We evaluated consecutive autopsy cases, deceased for COVID-19, from Italy between Apr 30, 2020 and Jan 18, 2021. We evaluated SARS-CoV-2 in cardiomyocytes, expression of ACE2 (total and glycosylated form), and transmembrane protease serine protease-2 (TMPRSS2) protein. In order to study the role of diabetes on cardiomyocyte alterations, independently of COVID-19, we investigated ACE2, glycosylated ACE2, and TMPRSS2 proteins in cardiomyocytes from DM and Non-DM explanted-hearts. Finally, to investigate the effects of DM on ACE2 protein modification, an in vitro glycation study of recombinant human ACE2 (hACE2) was performed to evaluate the effects on binding to SARS-CoV-2 Spike protein. The authors included cardiac tissue from 97 autopsies. DM was diagnosed in 37 patients (38%). Fourth-seven out of 97 autopsies (48%) had SARS-CoV-2 RNA in cardiomyocytes. Thirty out of 37 DM autopsy cases (81%) and 17 out of 60 Non-DM autopsy cases (28%) had SARS-CoV-2 RNA in cardiomyocytes. Total ACE2, glycosylated ACE2, and TMPRSS2 protein expressions were higher in cardiomyocytes from autopsied and explanted hearts of DM than Non-DM. In vitro exposure of monomeric hACE2 to 120 mM glucose for 12 days led to non-enzymatic glycation of four lysine residues in the neck domain affecting the protein oligomerization. Conclusions The upregulation of ACE2 expression (total and glycosylated forms) in DM cardiomyocytes, along with non-enzymatic glycation, could increase the susceptibility to COVID-19 infection in DM patients by favouring the cellular entry of SARS-CoV2.

Background/objectives Pericoronary adipose tissue inflammation might lead to the development and destabilization of coronary plaques in prediabetic patients. Here, we evaluated inflammation and leptin to adiponectin ratio in pericoronary fat from patients subjected to coronary artery bypass grafting (CABG) for acute myocardial infarction (AMI). Furthermore, we compared the 12-month prognosis of prediabetic patients compared to normoglycemic patients (NG). Finally, the effect of metformin therapy on pericoronary fat inflammation and 12-months prognosis in AMI-prediabetic patients was also evaluated. Methods An observational prospective study was conducted on patients with first AMI referred for CABG. Participants were divided in prediabetic and NG-patients. Prediabetic patients were divided in two groups; never-metformin-users and current-metformin-users receiving metformin therapy for almost 6 months before CABG. During the by-pass procedure on epicardial coronary portion, the pericoronary fat was removed from the surrounding stenosis area. The primary endpoints were the assessments of Major-Adverse-Cardiac-Events (MACE) at 12-month follow-up. Moreover, inflammatory tone was evaluated by measuring pericoronary fat levels of tumor necrosis factor-α (TNF-α), sirtuin 6 (SIRT6), and leptin to adiponectin ratio. Finally, inflammatory tone was correlated to the MACE during the 12-months follow-up. Results The MACE was 9.1% in all prediabetic patients and 3% in NG-patients. In prediabetic patients, current-metformin-users presented a significantly lower rate of MACE compared to prediabetic patients never-metformin-users. In addition, prediabetic patients showed higher inflammatory tone and leptin to adiponectin ratio in pericoronary fat compared to NG-patients (P < 0.001). Prediabetic never-metformin-users showed higher inflammatory tone and leptin to adiponectin ratio in pericoronary fat compared to current-metformin-users (P < 0.001). Remarkably, inflammatory tone and leptin to adiponectin ratio was significantly related to the MACE during the 12-months follow-up. Conclusion Prediabetes increase inflammatory burden in pericoronary adipose tissue. Metformin by reducing inflammatory tone and leptin to adiponectin ratio in pericoronary fat may improve prognosis in prediabetic patients with AMI. Trial registration Clinical Trial NCT03360981, Retrospectively Registered 7 January 2018

Aging accounts for increased risk and dismal outcome of ischemic stroke. Here, we investigated the impact of age-related changes in the immune system on stroke. Upon experimental stroke, compared with young mice, aged mice had increased neutrophil clogging of the ischemic brain microcirculation, leading to worse no-reflow and outcomes. Aged mice showed an enhanced granulopoietic response to stroke that led to the accumulation of CD101 + CD62L lo mature and CD177 hi CD101 lo CD62L lo and CD177 lo CD101 lo CD62L hi immature atypical neutrophils in the blood, endowed with increased oxidative stress, phagocytosis and procoagulant features. Production of CXCL3 by CD62L lo neutrophils of the aged had a key role in the development and pathogenicity of aging-associated neutrophils. Hematopoietic stem cell rejuvenation reverted aging-associated neutropoiesis and improved stroke outcome. In elderly patients with ischemic stroke, single-cell proteome profile of blood leukocytes identified CD62L lo neutrophil subsets associated with worse reperfusion and outcome. Our results unveil how stroke in aging leads to a dysregulated emergency granulopoiesis impacting neurological outcome. Bacigaluppi and colleagues report that the accumulation of atypical mature and immature neutrophil subsets and a dysregulated emergency granulopoiesis response in aged mice and humans affect the outcome of stroke.

Background and purpose: pericoronary fat over-inflammation might lead to the development and destabilization of coronary plaque in patients with pre-diabetes (PDM). Notably, pericoronary fat could over-express the sodium-glucose cotransporter 2 (SGLT2) and leptin, along with decreased sirtuin 6 (SIRT6) expression in PDM vs. normoglycemic (NG) patients undergoing coronary artery bypass grafting (CABG) for acute myocardial infarction (AMI). However, in the current study, we evaluated inflammatory markers, SGLT2, SIRT6, and leptin levels in pericoronary fat and, subsequently, 12-month prognosis comparing PDM to NG subjected to CABG for AMI. In addition, we evaluated in PDM patients the effects of metformin therapy on SIRT6 expression, leptin, and SGLT2 levels, and assessed its beneficial effect on nitrotyrosine and inflammatory cytokine levels. Methods: we studied AMI patients referred for CABG, divided into PDM and NG-patients. PDM patients were divided into never-metformin users and metformin users. Finally, we evaluated major adverse cardiac events (MACE) at a 12-month follow-up. Results: the MACE was 9.1% in all PDM and 3% in NG patients (p < 0.05). Metformin users presented a significantly lower MACE rate in PDM than never-metformin users (p < 0.05). PDM showed higher inflammatory cytokines, 3-nitrotyrosine levels, SGLT2, and leptin content, and decreased SIRT6 protein levels in pericoronary fat compared to NG-patients (p < 0.05). PDM never-metformin-users showed higher SGLT2 and leptin levels in pericoronary fat than current-metformin-users (p < 0.05). Conclusions: metformin therapy might ameliorate cardiovascular outcomes by reducing inflammatory parameters, SGLT2, and leptin levels, and finally improving SIRT6 levels in AMI-PDM patients treated with CABG.